The hypothesis of this proposal is that lithium treatment of adolescents with concomitant bipolar disorders (BPDS) and substance dependency disorders (SDDS) will prevent or reduce continued substance dependency. In order to test this hypothesis, we plan to perform a random assignment double-blind placebo-controlled study of lithium in subjects aged 12-18 years old who fit DSM-III-R criteria for SDDS and for BPDS (type I or II or mania) or major depressive disorder with the adoleacent predictors of a future bipolar course. The twelve week lithium study protocol will comprise a two week single-blind placel-)o washout phase and a ten week double-blind placebo-controlled phase. In order to have 60 subjects (30 active, 30 placebo) complete at least eight weeks of protocol, we expect to enter a minimum of 90 subjects due to the anticipated 20 percent rate of placebo washout response and 30 percent rate of drop-out. Baseline and week 8 and 12 evaluations will include psychiatric (SDDS and BPDS), family history, psychosocial, cognitive, school, physical and laboratory assessments. Weekly scheduled monitoring will include psychiatric (SDDS and BPDS) ratings, a lithium side effects scale, urine drug and alcohol screens and serum lithium levels. In addition, random weekly urine drug and alcohol screens and serum lithium levels will be obtained. Lithium dose will be predicted from a baseline single-dose 24-hour serum lithium level utilizing a nomogram and will then be adjusted (using a linear proportion), if needed, to obtain steady-state serum lithium levels of 0.9-1.3 mEq/L. Subjects will be re-evaluated at six months after completion of the lithium study. The high rate of morbidity and mortality of SDDS and of BPDS emphasize the importance of treatment research for the proposed study population. If lithium treatment is proven effective at the onset of these disorders during the teenage years, it would permit the adolescents to develop age-appropriate family, peer and school functioning rather than become chronically substance dependent with the attendent complications of incarceration, broken families, and suicide.